L-lysine hydrochloride (2,5.00 g, 27.4 mmol, 1.0 equiv) and methanol (30 mL, 0.9 M) were added to a round bottom flask. The suspension was heated to reflux until the solid was completely dissolved. Thionyl chloride (2.59 mL, 35.6 mmol, 1.3 eq.) was added slowly dropwise with a controlled drip time of 15 minutes. The reaction system was kept under reflux conditions for 17 hours. Upon completion of the reaction, most of the volatiles were removed by distillation (ca. 25 mL), followed by azeotropy with toluene under reduced pressure to remove the remaining volatiles to afford pure lysine methyl ester dihydrochloride (3, quantitative yield, white solid), which was used directly in the next step of the reaction without further purification. The physical and chemical properties of the resulting compound were analyzed to be consistent with the data reported in the literature.
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